Hartley et al (Journal of Medicinal Chemistry, Vol. 14, 895-896) discloses a method for resolution of salbutamol precursor by using tartaric acid derivatives such as di p-toluoyl tartaric acid.
U.S. Pat. No. 5,399,765 discloses a process for the preparation of optically pure (R)- and (S)-isomers by the resolution of a mixture of enantiomers of albuterol precursor, methyl 5-[2-[(1,1-dimethylethyl)amino]-1-hydroxyethyl]-2-hydroxy benzoate using a chiral acid as the resolving agent. The chiral acid is selected from the group consisting of (−) di-toluoyl-L-tartaric acid and (+)-di-toluoyl-D-tartaric acid. The process results into diastereomeric salt having 80-99% enantiomeric excess (e e) of desired enantiomers of albuterol, which on treatment with base liberates desired enantiomers of albuterol. The process is not cost-effective as the yield of optically pure R- and S-isomer is in the range of 21-43%.
U.S. Pat. No. 5,442,118 disclose a process for the preparation of optically pure (R)- and (S)-isomers of albuterol and similar ethanol amines by the asymmetric reduction of iminoketones with borane as reducing agent, such as borane-dimethyl sulfide or borane-tetrahydrofuran, in the presence of a chiral 1,3,2-oxazaborole catalyst. The process uses costly reagents and gives low optical purity of the order of 93-95% ee.
U.S. Pat. No. 6,365,756 discloses a process for the production of optically enriched (R)- or (S)-albuterol by first preparing a novel ketal derivative of albuterol, namely 2-(N-t-butylamino)-1-(+2,2-dimethyl-1,2-benzodioxin-6-yl)ethanol. The resolution is carried out with a chiral tartaric acid derivative such as (+) or (−) di-O-benzoyl tartaric acid or di-toluoyl tartaric acid. The process is a complicated multistage process involving resolution of the ketal derivative. The process also results into low enantiomeric excess of the order of 65% (based on the values given in the examples) and reduces its economic viability. This process also requires additional crystallization thereby lowering the overall yield.
WO2002/048090 discloses a process for the preparation of optically pure (R)- and/or (S)-salbutamol by resolving a racemic or optically impure mixture of enantiomers of salbutamol or its precursor by using chiral acid, (L)- or (D)-tartaric acid. The process results into good enantiomeric excess. The resolving agent is not recovered and reused. The undesired (S)-isomer salbutamol is also not converted into desired (R)-isomer.
WO2005/113481 discloses a process for the preparation of (R)-Salbutamol. A mixture of racemic salbutamol is treated with D-di-benzoyl tartaric acid, in the ratio of 1:0.5 to 1.3 mol and in the presence of C1 to C4 alcohol to obtain (R)-Salbutamol.D-di-benzoyl tartaric acid. The crude product is crystallized by seeding with (R) Salbutamol. D-di-benzoyl tartaric acid. The product is further recrystallized in methanol. The process results into high enantiomeric excess but low overall yield (based on the values given in the examples) and is not therefore, economically viable.
U.S. Pat. No. 7,049,469 discloses a process for preparing (R)-salbutamol. The process comprises of asymmetric hydrogenation of prochiral salbutamone in the presence of Rhodium and a chiral bidentate phosphine ligand as catalyst system. The process utilizes very costly catalyst and results into low enantiomeric excess. Costly reagent and low enantiomeric excess reduce the feasibility of the process on industrial scale
Most of the prior art processes in general do not recover and reuse the resolving agent, thereby rendering them costly. Despite the many attempts of the prior art to prepare optically pure salbutamol, there is still need to develop processes, which are cost-effective without sacrificing the optical purity of Salbutamol.